It is the goal of this Program to understand how components of the cell membrane and membrane-associated macromolecules serve as regulators of cell function, and how changes in these components with development result in the achievement of definitive functional states in excitable cells. Our specific aims are: 1) to characterize the ionic currents in the embryonic ventricle, and to determine how the observed changes in macroscopic properties of these currents during development are reflected in alterations in properties of the membrane channels; b) to perfect the patch electrode clamp technique for measuring current through individual ionic channels in heart cell membranes and to determine the single channel conductance and open-close kinetics of these channels; c) to define the mechanism of action of insulin on aminoacid transport across the developing embryonic chick heart cell membrane and to characterize the regulation and biochemistry of the insulin receptor(s) of the chick heart cell; d) to understand the genetic control of insulin receptors and the biochemical responses that result from their occupancy; e) the elucidate the mechanisms by which acetylcholine induces a hyperpolarizing K current that is responsible for decreasing the frequency of the heartbeat; f) to understand the mechanism by which junctional channels are formed between newly apposed heart cells. The Program consists of five inter-related projects subserved by four core facilities.